Inflammation, the most immediate hematologic response, is the first line of defense against invading microbes. It also initiates the cascade of events leading to longer lasting adaptive immunity. Maintenance of hematologic stasis is critical, and excessive inflammation can lead to destructive attacks against self. Unresolved inflammation can also predispose the host to some forms of cancers, and the host response to these malignancies show parallels to the traditional paradigms of inflammation in wound healing. Up- regulation of the ST6Gal-1 sialyltransferase is an integral part of the systemic inflammatory response, and there is potential diagnostic value for elevated sialylation status in inflammatory pathologies. However, the contribution of ST6Gal-1 in the inflammatory process remains elusive. Our Preliminary Data demonstrate novel contributions for ST6Gal-1 related to myelopoissis, neutrophil margination/demargination, and acute neutrophilic inflammation. The fact that peritoneal leukocytosis was increased following challenge with an infectious agent and a sterile irritant upon ST6Gal-1 deficiency points to an intrinsic role of ST6Gal-1 in acute inflammation. Experiments using epinephrine challenge to elicit demargination demonstrated a significantly expanded pool of marginated neutrophils upon ST6Gal-1 deficiency. ST6Gal-1 deficient mice also had a strikingly enhanced capacity to recoverfrom cyclophosphamide-induced myelosuppression. By constructing a mutant mouse with a deletion in P1 (Siat1kP'\), one of six major promoters regulating expression of the ST6Gal-1 gene, we demonstrated the requirement for ST6Gal-1 for inflammatory cell functionality is mediated by the P1 promoter. We hypothesize that ST6Gal-1, presumably by a2,6-sialyl modifications of terminal glycan structures, serves as a regulator in inflammatory cell functionality and in maintenance of hematologic stasis. We shall elucidate the mechanistic basis of how, and to what extent these processes are modulated by ST6Gal-1 by determining 1) the specific ways inflammatory cell functionality impacted upon ST6Gal-1 deficiency, 2) the developmental- and cellular-range of utilization of the P1 promoter, 3) where ST6Gal-1 expression is important for inflammatory cell function, and 4) how the sialyl-glycan architecture is altered when ST6Gal-1 is deficient, and how such alterations may impact on function. These studies will increase our understanding of how ST6Gal-1 modulates circulating neutrophil number and function. These studies will also shed light on the role of ST6Gal-1 in mediating recoveryfrom chemotherapy following cytotoxic antineoplastic therapy.